Measurement of Body Composition in Pancreatic Cancer: A Systematic Review, Meta-Analysis, and Recommendations for Future Study Design.

BACKGROUND/OBJECTIVES: Sarcopenia in pancreatic cancer may increase the risk of chemotherapy-related toxicity and post-operative morbidity. This systematic review and meta-analysis aimed to quantify the prevalence of sarcopenia in early stage pancreatic cancer. METHODS: Relevant studies were identified using Ovid Medline and Elsevier Embase. Pooled estimates of prevalence rates (percentages) and corresponding 95% confidence interval (CI) were computed using a random-effects model to allow for heterogeneity between studies. RESULTS: The majority of the 33 studies (n = 5,593 patients) included in this meta-analysis utilized computed tomography (CT)-derived measures for body composition assessment in patients undergoing pancreatic resection. Reported prevalence of sarcopenia varied between 14 and 74%, and the pooled prevalence was 39% (95% CI: 38-40%) Heterogeneity was considerable, however, (I2 = 93%) and did not improve significantly when controlling for assessment method, and use of pre-defined cut-offs for sarcopenia, limiting potential to evaluate the true impact of sarcopenia. CONCLUSION: The ready availability of sequential CT offers a valuable opportunity for body composition assessment, but the quality of assessment and interpretation must improve before the impact of body composition on treatment-related outcomes and survival can be assessed. We suggest recommendations for the assessment of body composition for the design of future studies.

Dietary intake in patients with chronic pancreatitis: A systematic review and meta-analysis.

BACKGROUND: A progressive reduction in the secretion of pancreatic enzymes in patients with chronic pancreatitis (CP) results in malabsorption and ultimate malnutrition. However, the pathogenesis of malnutrition is multifactorial and other factors such as chronic inflammation, alcohol excess and poor dietary intake all contribute. Patients may restrict their dietary intake due to poor appetite or to avoid gastrointestinal symptoms and abdominal pain. Whilst up to half of patients with chronic pancreatitis are reportedly malnourished, the dietary intake of patients with CP is relatively understudied and has not been systematically reviewed to date. AIM: To perform a systematic review and meta-analysis of the dietary intakes of patients with CP compared to healthy controls, and to compare the dietary intake of patients with alcohol-related CP and non-alcohol-related CP. METHODS: A systematic literature search was performed using EMBASE, MEDLINE, and Cochrane review on studies published between 1946 and August 30th, 2019. Adult subjects with a diagnosis of CP who had undergone dietary assessment were included in the systematic review (qualitative analysis). Studies on patients with other pancreatic diseases or who had undergone pancreatic surgery were not included. Studies comparing the dietary intake of patients with CP to that of healthy controls were included in the meta-analysis (quantitative analysis). Meta-analysis was performed using Review Manager 5.3. Newcastle Ottawa Scale (NOS) was used to assess quality of studies. RESULTS: Of 6715 studies retrieved in the search, 23 were eligible for qualitative analysis while 12 were eligible for quantitative analysis. In the meta-analysis, the total energy (calorie) intake of patients with CP was similar to that of healthy controls [mean difference (MD): 171.3; 95% confidence interval (CI): -226.01, 568.5; P = 0.4], however patients with CP consumed significantly fewer non-alcohol calories than controls [MD: -694.1; 95%CI: -1256.1, (-132.1); P = 0.02]. CP patients consumed more protein, but carbohydrate and fat intakes did not differ significantly. Those with alcohol-related CP consumed more mean (standard deviation) calories than CP patients with a non-alcohol aetiology [2642 (1090) kcal and 1372 (394) kcal, respectively, P = 0.046], as well as more protein, fat, but not carbohydrate. CONCLUSION: Although patients with CP had similar calorie intake to controls, studies that analysed the contribution of alcohol to energy intake showed that patients with CP consumed fewer non-alcohol calories than healthy controls. A high calorie intake, made up to a large degree by alcohol, may in part contribute to poor nutritional status in CP.

Characterising the impact of body composition change during neoadjuvant chemotherapy for pancreatic cancer.

BACKGROUND: Pancreatic Cancer remains a lethal disease for the majority of patients. New chemotherapy agents such as Folfirinox offer therapeutic potential for patients who present with Borderline Resectable disease (BRPC). However, results to date are inconsistent, with factors such as malnutrition limiting successful drug delivery. We sought to determine the prevalence of sarcopenia in BRPC patients at diagnosis, and to quantify body composition change during chemotherapy. METHODS: The diagnostic/restaging CT scans of BRPC patients were analysed. Body composition was measured at L3 using Tomovision Slice-O-Matic™. Total muscle and adipose tissue mass were estimated using validated regression equations. Sarcopenia was defined as per gender- and body mass index (BMI)-specific lumbar skeletal muscle index (LSMI) and muscle attenuation reference values. RESULTS: Seventy-eight patients received neo-adjuvant chemotherapy, and 67 patients underwent restaging CT, at which point a third were deemed resectable. Half were sarcopenic at diagnosis, and sarcopenia was equally prevalent across all BMI categories.. Skeletal muscle and adipose tissue (intra-muscular, visceral and sub-cutaneous) area decreased during chemotherapy (p < 0.0001). Low muscle attenuation was observed in half of patients at diagnosis, and was associated with increased mortality risk. Loss of lean tissue parameters during chemotherapy was associated with an increased mortality risk; specifically fat-free mass, HR 1.1 (95% CI 1.03-1.17, p = 0.003) and skeletal muscle mass, HR 1.21 (95%CI 1.08-1.35, p = 0.001). CONCLUSIONS: Sarcopenia was prevalent in half of patients at the time of diagnosis with BRPC. Low muscle attenuation at diagnosis, coupled with lean tissue loss during chemotherapy, independently increased mortality risk.

The potential role of gut microbiota in pancreatic disease: A systematic review.

BACKGROUND: Several studies have suggested a link between microbiota imbalance and some gastrointestinal, inflammatory and neoplastic diseases. However, the role in pancreatic diseases remain unclear. To evaluate the available evidence for pancreatic diseases, we undertook a systematic review. METHODS: OVID Medline (1946-2017), EMBASE (1980-2017) and the Cochrane Central Register of Controlled Trials (CENTRAL Issue 3, 2017) were searched for studies on microbiota in pancreatic disease. We also searched the reference lists of retrieved papers, and conference proceedings. We excluded animal studies, reviews, and case reports. RESULTS: A total of 2833 articles were retrieved. After screening and applying the exclusion criteria, 10 studies were included. Three studies showed lower levels of Bifidobacterium or Lactobacillus and higher levels of Enterobacteriaceae in chronic pancreatitis. Two of these studies were uncontrolled, and the third (controlled) study which compared patients with endocrine and exocrine insufficiency, reported that Bacteroidetes levels were lower in those patients without diabetes, while Bifidobacteria levels were higher in those without exocrine insufficiency. Only one study investigated acute pancreatitis, showing higher levels of Enterococcus and lower levels of Bifidobacterium versus healthy participants. There was an overall association between pancreatic cancer and lower levels of Neisseria elongate, Streptococcus mitis and higher levels of Porphyromonas gingivalis and Granulicatella adiacens. CONCLUSIONS: Current evidence suggests a possible link between microbiota imbalance and pancreatic cancer. Regarding acute and chronic pancreatitis, data are scarce, dysbiosis appears to be present in both conditions. However, further investigation is required to confirm these findings and to explore therapeutic possibilities.